Introduction: Methotrexate (MTX), Moringa oleifera (MO), and Andrographis paniculata (AP) have been reported to have anti-hyperglycemic, antioxidative, and anti-inflammatory effects in diabetic rats. This study aims to investigate the single and combination effects of MTX, MO, and AP on random blood glucose levels, interleukin-6 (IL-6) levels, and trabecular density in diabetic rats. Methods: A total of 49 male rats were divided into seven groups, namely one control group and six diabetes mellitus (DM) groups. All rats in the DM groups were injected with streptozotocin-nicotinamide (STZ-NA) intraperitoneally. In addition, the DM groups were administered with a placebo daily (DG), a single dose of 500 mg/kg BW MO daily (DG+MO), a single dose of 500mg/kg BW AP daily (DG+AP), a single dose of 7 mg/kg BW MTX once a week (DG+MTX), a combination of MTX+MO, and a combination MTX+AP, respectively. The experiment lasted for 28 days. On day 29, the right and left femur of the rats were collected for IL-6 examination (ELISA) and histopathological analysis. Results: IL-6 expression levels were significantly lower in diabetic rats treated with single and combination of MTX, MO, and AP compared to untreated diabetic rats (p < 0.05). However, the random blood glucose levels and trabecular density between treated and untreated diabetic rats were not significantly different (p < 0.001, p = 0.152). In addition, IL-6 levels were not correlated with trabecular density in all groups (r = -0.057, p = 0.722). Conclusion: Single doses of MTX, MO leaf extract, and AP leaf extract could suppress IL-6 expression in the femur tissue in diabetic rats. However, the IL-6 expression was not correlated with trabecular density although it significantly affected blood glucose levels in this study.

Objective: To investigate the cardioprotective effect of Saffron (Crocus sativus L.) treatment as a potential supplement on patients with type 2 diabetes mellitus (T2DM). Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to analyze articles retrieved from PubMed, ScienceDirect, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and China Biology Medicine (CBM) with a publication time span from January 15, 2015 to March 20, 2023. The articles were published in English only, including randomized controlled trials (RCTs) on adult patients who were diagnosed with T2DM, and received either Saffron or placebo treatment. Meta-analysis was performed using Review Manager 5.4 software. The present study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) with a registration number as CRD42023443180. Results: Seven RCTs with 455 patients were included in the study. The data revealed that Saffron treatment significantly reduced tumor necrosis factor (TNF)-α (P = 0.008) and fasting blood glucose (FBG) (P = 0.04) levels compared with what placebo did in T2DM patients. No significant differences were shown in the levels of interleukin (IL)-6, malondialdehyde (MDA), high serum C-reactive protein (hs-CRP), lipid profile, blood pressure, and body mass index (BMI) between Saffron and placebo ( P > 0.05) . Conclusion Saffron treatment has a cardioprotective effect in T2DM patients by reducing TNF-α and FBG levels. However, the potential anti-oxidant, anti-hypertensive, and anti-dyslipidaemia effects of the phytochemical need to be further investigated.